Genetic loci associated with C-reactive protein levels and risk of coronary heart disease
Elliott P et al. – Lack of concordance between the effect on coronary heart disease risk of C-reactive protein (CRP) genotypes and CRP levels argues against a causal association of CRP with coronary heart disease. Methods- Study of the association of genetic loci with CRP levels and risk of coronary heart disease
- Genome-wide association (n = 17,967) and replication study (n = 13,615) to identify genetic loci associated with plasma CRP concentrations
- Data collection between 1989-2008 and genotyping between 2003-2008
- Mendelian randomization study of most closely associated single-nucleotide polymorphism (SNP) in CRP locus and published data on other CRP variants (total 28,112 cases; 100,823 controls)
- Investigation of association of CRP variants with coronary heart disease
- Comparison of finding with that predicted from meta-analysis of observational studies of CRP levels and risk of coronary heart disease
- For other loci associated with CRP levels, selection of most closely associated SNP for testing against coronary heart disease among 14,365 cases and 32,069 control
- Main outcome measure: risk of coronary heart disease
Results- Polymorphisms in 5 genetic loci strongly associated with CRP levels (% difference per minor allele): SNP rs6700896 in LEPR, rs4537545 in IL6R, rs7553007 in CRP locus, rs1183910 in HNF1A, and rs4420638 in APOE-CI-CII
- Association of SNP rs7553007 in CRP locus with coronary heart disease: odds ratio (OR) of 0.98 per 20% lower CRP level
- Mendelian randomization study of variants in CRP locus showed no association with coronary heart disease
- SNPs rs6700896 in LEPR, rs4537545 in IL6R, and rs4420638 in APOE-CI-CII cluster all associated with risk of coronary heart disease
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